The functional capacity of genetically encoded proteins is powerfully expanded by reversible posttranslational modification. Within eukaryotic cells, the regulation of gene expression is intimately linked with posttranslational modification of histone proteins. Reversible histone posttranslational modifications include acetylation of lysine, phosphorylation of serine and threonine, and methylation of lysine and arginine. The resulting complexity of modifications has been postulated to act as a ‘histone code,’ by which these patterns of modifications are ‘read’ by cellular machinery to produce a specific gene regulatory outcome.
One class of human enzymes capable of demethylating lysine residues includes the amine oxidase domain-containing lysine specific demethylase 1 (LSD1). Catalysis by LSD1 is a flavin-dependent process in which formaldehyde and peroxide are produced as by-products of histone demethylation. The amine oxidase domain of LSD1 is homologous to equivalent domains found in monoamine oxidases A and B (MAO A, 17.6% identity; MAO B, 17.6% identity). Inhibitors of LSD1 and/or of monoamine oxidases A and B may have therapeutic utility.